We are looking for a postdoctoral fellow to join our team Biology of the NeuroMuscular System headed by Fred Relaix at the IMRB (Créteil, France; 20 min from Paris by public transport), which offers an international environment with an easy access to core facilities and a strong network of multidisciplinary collaborations. Our lab is located in a brand-new building on the campus of the Alfort school of veterinary medicine (Maisons-Alfort, France; 20 min from Paris by public transport).
Keywords: mitochondrial diseases, mitochondrial membranes, respiratory coupling, metabolism, obesity, mouse genetics
Mitochondrial diseases form a large group of congenital diseases characterized by deficient mitochondrial efficiency that compromises the function of vital organs and locomotion. We have recently found that mutation of the Hacd1 gene leads to a mitochondrial myopathy and identified that this gene is a key player of respiratory coupling in skeletal muscle, through the regulation of the lipid composition of mitochondrial membranes (Prola et al., Science Advances, 2021).
Unexpectedly, we found that this muscle-specific reduction in mitochondrial coupling leads to an elevated basal metabolism that protects Hacd1 mutant mice against diet-induced obesity. This observation challenges the classical view in which a reduction in mitochondrial coupling efficiency is necessarily detrimental to health and we have first evidence that a fine tuning of HACD1 activity could confer a metabolic advantage yet preserving muscle function.
The project will thus aim at developing genetic strategies to improve both mitochondrial diseases and morbid obesity through the modulation of Hacd1 expression. For this, you will set up an AAV-driven expression of Hacd1 in two different mouse models of mitochondrial diseases. Reciprocally, you will test the capacity of Hacd1 silencing at preventing and eventually curing diet-induced obesity by developing a conditional knockout or an antisense oligonucleotide strategy for Hacd1 gene. Readouts of these strategies will include metabolic and locomotor assessments as well as histological and biochemical analyses.
Profile: You have a strong interest in mitochondria or muscle biology, and you have a solid expertise in mouse genetics or molecular biology. You work with rigor and creativity, and you are an appreciated teammate.
Position: The postdoctoral position is fully funded for one year by the Association Française contre les Myopathies, with the possibility to be extended for one or two years and with a starting date ideally in April 2022.
To apply, please send a cover letter, CV and contact information for 2 references to firstname.lastname@example.org